The first treatment for type 2 diabetes is often meal planning for blood glucose (sugar) control, weight loss, and exercising. Sometimes these measures are not enough to bring blood glucose levels down near the normal range. The next step is taking a medicine that lowers blood glucose levels.

High levels of glucose in people with Diabetes occur because glucose remains in the blood rather than entering cells, where it belongs. But for glucose to pass into a cell, insulin must be present and the cell must be "hungry" for glucose.

People with type 1 diabetes don't make insulin. For them, insulin shots are the only way to keep blood glucose levels down.

People with type 2 diabetes tend to have two problems: they don't make quite enough insulin and the cells of their bodies don't seem to take in glucose as eagerly as they should.

All diabetes pills sold today are members of five classes of drugs: sulfonylureas, meglitinides, biguanides, thiazolidinediones, and alpha-glucosidase inhibitors. These five classes of drugs work in different ways to lower blood glucose levels.

Sulfonylureas
Sulfonylureas stimulate the beta cells of the pancreas to release more insulin. Sulfonylurea drugs have been in use since the 1950s.  Most used are Glibenclamide (ie Glynase NB generic name in US = glyburide) Gliclazide (Diamicron), and glimepiride (Amaryl). These drugs are generally taken one to two times a day, before meals. All sulfonylurea drugs have similar effects on blood glucose levels, but they differ in side effects and how often they are taken.

Meglitinides
Meglitinides are drugs that also stimulate the beta cells to release insulin but are short acting compared to sulfonylurea’s. Repaglinide (Novonorm) is used locally. They are taken before each of three meals.

Because sulfonylureas and meglitinides stimulate the release of insulin, it is possible to have hypoglycemia (low blood glucose levels).

Biguanides
Metformin (brand name Glucophage) is a biguanide. Biguanides lower blood glucose levels primarily by decreasing the amount of glucose produced by the liver. Metformin also helps to lower blood glucose levels by making muscle tissue more sensitive to insulin so glucose can be absorbed. It is usually taken two times a day. A side effect of metformin may be diarrhea, but this is improved when the drug is taken with food.

Thiazolidinediones
Rosiglitazone (Avandia) and pioglitazone (ACTOS) are in a group of drugs called thiazolidinediones. These drugs help insulin work better in the muscle and fat and also reduce glucose production in the liver a similar effect as metformine.  Both drugs are effective at reducing A1C and generally have few side effects. Both drugs appear to increase the risk for heart failure in some individuals, and there is debate about whether rosiglitazone may contribute to an increased risk for heart attacks. Monitoring the choice of patient should avoid this possible risk.

DPP-4 Inhibitors
A new class of medications called DPP-4 inhibitors help improve A1C without causing hypoglycemia. They work by by preventing the breakdown of a naturally occuring compound in the body, GLP-1. GLP-1 reduces blood glucose levels in the body, but is broken down very quickly so it does not work well when injected as a drug itself.  DPP-4 inhibitors do not tend to cause weight gain and tend to have a neutral or positive effect on cholesterol levels. Sitagliptin (Januvia) is currently the only DPP-4 inhibitor on the market and recently introduced locally.

Alpha-glucosidase inhibitors
Acarbose  and meglitol  are alpha-glucosidase inhibitors. These drugs help the body to lower blood glucose levels by blocking the breakdown of starches, such as bread, potatoes, and pasta in the intestine. They also slow the breakdown of some sugars, such as table sugar. Their action slows the rise in blood glucose levels after a meal. They should be taken with the first bite of a meal. These drugs may have gastro-intestinal side effects, mainly gas and diarrhea.

Oral combination therapy
Because the drugs listed above act in different ways to lower blood glucose levels, they may be used together. For example, a biguanide and a sulfonylurea may be used together. 

 

Can diabetes pills help me?
Only people with type 2 diabetes can use pills to manage their diabetes. These pills work best when used with meal planning and exercise. This way you have three therapies working together to lower your blood glucose levels.

Diabetes pills sometimes stop working after a few months or years. The cause is often unknown. This doesn't mean your diabetes is worse. When this happens, oral combination therapy can help.

Even if diabetes pills do bring your blood glucose levels near the normal range, you may still need to take insulin if you have a severe infection or need surgery. Pills may not be able to control blood glucose levels during these stressful times when blood glucose levels shoot up.

 

What about insulin?
Although it is a common practice to try pills before insulin, you may start on insulin based on several factors.

These factors include:

Because diabetes pills seem to help the body use insulin better, some people take them along with insulin shots. The idea behind this "combination" therapy is to try to help insulin work better.

Premixed insulin can be helpful for people who have trouble drawing up insulin out of two bottles and reading the correct directions and dosages. It is also useful for those who have poor eyesight or dexterity and is a convenience for people whose diabetes has been stabilized on this combination. The most used premixed insulin is Mixtard 30/70. This insulin is being replaced currently by Novomix 30/70 in the Flexpen.
Actrapid is being replaced with Novo Rapid. Reason is that the rapid acting insulines have a more natural action profile and mimick the body’s response to meals better.  Change over will be 1:1.

Characteristics of Insulin
The three characteristics of the four types of insulin are onset, peaktime, and duration.

With the help of your doctor or nurse, you can find an insulin routine that will keep your blood glucose near normal, help you feel good, and fit your lifestyle.
Most people with type 2 diabetes may need one injection per day without any diabetes pills. Some may need a single injection of insulin in the evening (at supper or bedtime) along with diabetes pills. Sometimes diabetes pills stop working, and people with type 2 diabetes will start with two injections per day of two different types of insulin. They may progress to three or four injections of insulin per day.
Many people who take insulin use a syringe. Other choices are insulin pens and pump therapy. Some insulin pens contain a cartridge of insulin that is inserted into the pen and some come already filled with insulin (Novolet or Flexpen) and are discarded after all the insulin has been used. The insulin dose is dialed on the pen, and the insulin is injected through a needle, much like using a syringe.